PDMS is a common material for fabrication of microfluidic devices. Elasticity provided by PDMS enables the formation of active devices which can utilize pressurized membranes such as pumps and mixers. However, for microfluidic structures requiring dimensional stability, rigidity, or disposability, PDMS is not the preferred candidate. Such properties are provided by plastics.
Plastics can be manufactured using mass fabrication technologies such as injection molding and hot embossing with well established bonding processes but at the cost of sacrificing active device functionality. Therefore a combination of PDMS and plastics is desirable in the fabrication processes of microfluidic devices in order to gain the advantages of both materials as described above. Fabrication process combining plastic substrates with PDMS membranes enables the formation of active microfluidic devices inside dimensionally stable systems, merging the functionality of PDMS with established plastic fabrication technologies.
Irreversible bonding between PDMS and plastics for fluidics require interfaces which can handle high pressure and harsh chemical environments. Hydrolytic stability under acidic or basic conditions is particularly important for chemical reactions as well as for cell growth. While direct bonding between PMMA and PDMS has been explored, results indicated that direct interfaces only withstood a pressure of approximately 2.5 psi before failure.
To improve bond strength between dissimilar materials, primers are most commonly used. Primers are molecules or films of molecules which are sandwiched between the two dissimilar materials. Such primers comprise at least two functionalities. One function is used to enhance the bond to one material while the other function is used to enhance the bond to the other material. In the case of PDMS bonding to plastics, such primers consist of a silicon-carbon bond, with the carbon atom linked to organic groups such as amide or vinyl groups. These groups provide covalent bonds with organic substrates such as plastics and polymers. Additionally, the silicon atom is bonded to hydrolysable ethyl or methyl groups which can react with other silanols present on the PDMS surface or with metal oxides thus forming inorganic covalent bonds.
Polycarbonate (PC) and polymethylmethacrylate (PMMA) surfaces have been shown to react with amine functional silanes such as AminoPropylTriEthoxySilane (APTES) to form amide bonds on the surface. These silanes then crosslink into a polymer leaving ethyl or methyl groups on the surface. Such silanes were used as primers and have been shown to plasma-bond to PDMS. However, it was found that exposing monolayer primer coatings to plasma bonding processes resulted in degradation of the silane films, leading to DI water induced bond failure and delamination under pressure conditions below 15 psi.
PDMS has greatly reduced the entrance barrier for research in microfluidics based chemistry and biology. The introduction of the elastic microvalve has led to the creation of highly integrated systems capable of automated experimentation, with examples such as whole blood PCR analysis, microbial cell culture, protein crystallization, and multicellular manipulation and analysis, and particle production.
However, for actuated microfluidics to transition from customized prototype devices to industrial scale device production, a transition must be made from elastomers to plastics. Plastics can be manufactured using mass fabrication technologies such as injection molding and hot embossing with well established bonding processes. Plastics are also more dimensionally stable, rigid, and chemically resistant.
Plastics may provide many benefits for microfluidic devices not offered by PDMS. Rigidity enables a variety of reliable external interface options, such as manifold integration, direct barbed tubing connections, and gasket connectors. Additionally, integrating flexible membranes into rigid plastics will enable a variety of new devices currently not possible in PDMS due to chip elasticity such as large area or high pressure membrane deformation, on-chip pressure regulators, full volume pumps, and reliable square channel membrane valve particle filters.
Few technologies exist for bonding PDMS to plastics, notably CVD processes or silane/silicate coatings. Also, data on bond strength in aqueous and chemically harsh environments is not available for the published processes. A bonding process which can demonstrate bonds on low temperature plastics with long term hydrolytic stability is critical for the creation of plastic devices with active membranes. This process would enable active microfluidic devices inside dimensionally stable systems, merging the functionality of PDMS with established plastic mass fabrication technologies.
Bonding Technologies
Bonding between PDMS and plastics for fluidics requires interfaces which can handle high pressure and harsh chemical environments. Typical pressures for total valve closure lie between 5 and 15 psi. Of all possible properties of bond strength, hydrolytic stability is particularly important for reliability since cell growth, chemical synthesis, and protein crystallization, to name a few, all rely on aqueous environments with varying chemistries.
While direct bonding between PMMA and PDMS has been explored, results indicated that interfaces only withstood 2.5 psi before failure. Bond strength can be improved through an intermediate layer, such as a deposited film of glass. Two major methods have been attempted for intermediate layer deposition, direct deposition of glass onto the plastic surface and organo-functional-silane deposition. Direct glass deposition processes are high temperature activated or plasma activated, which can lead to plastic substrate breakdown. In addition, direct glass deposition onto plastic substrates leads to bonds which hydrolyze readily upon exposure to moisture. An intermediate coating containing an inorganic oxide or an organo-functional-silane to improve bond characteristics between organic and inorganic substrates was used. Primer compositions for improving adhesion are sold commercially, with one specifically for Sylgard 184 under the name Dow Corning 92-023 Primer, which contains a titanium alkoxide and allyltrimethoxysilane. However, bond chemistry between this primer and organic surfaces is non-ideal due to oxygen coupled bonds and the lack of long-term hydrolytic stability in aqueous environments, with the majority of the primer consisting of a titanium alkoxide, which readily absorbs water molecules.
More hydrolytically stable silane bonding systems have been explored for plastics, namely APTES to Polycarbonate (PC) and PMMA surfaces to improve the adhesion of sol-gel coatings. It was shown that PC surfaces react with amine groups of AminoPropylTriEthoxySilane (APTES) to form amide bonds on the surface directly. Since amide bonds are hydrolytically stable over a wide pH range, from −1 to greater than 15, amine functional silanes are excellent candidates for surface coatings. Bonding of these coatings to PDMS has also been demonstrated, but hydrolytic stability was not tested. Identifying the processes which cause hydrolytic failure in silane coatings will aid in developing silane compositions and process conditions necessary to ensure hydrolytic resistance.
Silanes and Bond Failure
An overview of silane is needed in order to understand the mechanisms for hydrolysis-induced bond failure. An organo-functional silane is a molecule comprising a silicon atom with at least one bond to carbon to enable organic functionality as shown in FIG. 7. The inorganic side of the silane molecule consists of a silicon atom bound to alkoxy groups through Si—O—C linkages. Commercially, the hydrolytic instability of these bound alkoxy groups allows silanes to hydrolyze in the presence of water, converting the bound alkoxy groups to hydroxyl groups while liberating alcohol molecules. These hydrolyzed silanes can then be used in sol-gel processing, condensing onto hydroxyl containing surfaces or with each other to form substrate bound films. Since the silane matrix looks similar to glass, it is an excellent candidate for plasma bonding to PDMS. In one embodiment, a silane derivative comprises or consists of a silane molecule as described above.
While amine functional silanes have been demonstrated to react directly with certain substrates such as PC and PMMA, prolonged treatment times necessary to generate a reasonable surface bond density as well as substrate selective chemistry make such a process not generally useful. As such, surface activation such as plasma or chemical treatments will be required. In general, these activated organic substrates will contain bound hydroxyl, carboxyl, or other ionic groups which promote hydrogen or ionic bonding of silanes to the organic surface. For activated organic substrates, silane alkoxy group hydrolysis into silanols poses a major problem. While bonding between the silanol group and surface hydroxyl groups is desired for coupling silanes to glass or oxides, bonds formed with organic substrates generate Si—O—C bonds, which are hydrolytically unstable (FIG. 8a). These are the same bonds formed between the silicon molecule and its original alkoxy group, which are meant to hydrolyze readily in water. Any contact with water after bond formation will result in Si—O—C bond hydrolysis and ultimately bond failure. Furthermore, Si—O—C bonds have also been found to form directly between alkoxy groups such as methoxy and surface hydroxyl groups via alcoholysis (FIG. 8b).
In order to achieve hydrolytically stable bonds between silanes and organic surfaces, bonds must be formed through reactions between the organofunctional groups (nitrogen containing) of the silane molecules and the organic surface (FIG. 8c).
In addition to the organic bond between the organofunctional-silane and the organic surface, other processes contribute to bond stability. Hydrolytic bond failure can occur at three locations in the bonding structure, at the PC-silane interface, at the PDMS-silane interface, and in the silane network itself as shown in FIG. 9. While direct interface hydrolysis is unlikely due to the stability of the amide bond, any hydrophilic groups at the interface can act as nucleation sites for water condensation, allowing the silane network near the interface to be plasticized and weakened. A similar process can occur at the PDMS-silane interface but with the possibility of hydrolysis directly at the interface in addition to the weakening of the silane network. For the silane network itself, high crosslink density can provide a major increase in resistance. However, networks formed by typical silanes, containing three silanol groups, tend to be cyclic, decreasing their resistance to dissolution. Addressing failure mechanisms in all three locations is necessary to ensure hydrolytic stability.